NorthWest Biotherapeutics Inc (NWBO)

[Slave1]

Flipper,

Here is the exact source you asked for, with no interpretation layered on top of it:

https://health.ec.europa.eu/system/files/2022-08/20220825_gmp-an1_en_0.pdf

The requirement for Grade C environments comes directly from Annex 1 of the EU GMP Guide, which MHRA enforces for all ATMP manufacturing. This is the governing rulebook for sterile and aseptic manufacturing in the UK.

Annex 1, Section 4.4 defines the purpose of Grade C:

“Grade C and D: These are cleanrooms used for carrying out less critical stages in the manufacture of aseptically filled sterile products…”

— Page 7

And Annex 1, Table 4 gives concrete examples of the operations that must take place in Grade C:

“Grade C – Preparation of solutions to be filtered including sampling and dispensing.”

— Table 4, Page 22

These are the upstream steps in any aseptic workflow. They are not permitted in Grade B because Grade B is defined as the background cleanroom for Grade A aseptic filling.

Now look at what NWBO reported:The company stated that the “full SOW 8 validation package was completed and accrued.”

A full validation package necessarily includes all upstream preparatory operations prior to the aseptic fill, including solution preparation, sampling, dispensing, process qualification activities and associated sterility assurance work. Annex 1 assigns those upstream activities to Grade C.

So when the filing states that SOW 8 was completed, the required regulatory environment is already defined by Annex 1. Those steps cannot legally occur entirely in Grade B and cannot occur in unclassified or unfinished space. They must take place in Grade C.

Once you apply the actual rulebook, the logic is unavoidable:

SOW 8 was completed.A full validation package includes upstream steps.Upstream steps must occur in Grade C.Therefore Grade C rooms had to exist, be qualified and be licensed at the time SOW 8 was performed.

That conclusion comes straight from Annex 1.Not from interpretation.Not from opinion.Not from NWBO.From the governing GMP regulation itself.

The source is:

EU GMP Annex 1Section 4.4 (definition of Grade C)Table 4 (examples of operations requiring Grade C)

This is the exact-source answer you requested.